Dataset Information

Inhalational exposures in patients with fibrotic interstitial lung disease: Presentation, pulmonary function and survival in the Canadian Registry for Pulmonary Fibrosis.

ABSTRACT:

Background and objective

Inhalational exposures are a known cause of interstitial lung disease (ILD), but little is understood about their prevalence across ILD subtypes and their relationship with pulmonary function and survival.

Methods

Patients with fibrotic ILD were identified from the multicentre Canadian Registry for Pulmonary Fibrosis. Patients completed questionnaires regarding ILD-related occupational and environmental exposures. The relationship between exposures and the outcomes of baseline age, gender, family history, pulmonary function and survival was analysed using linear and logistic regression models, linear mixed-effect regression models and survival analysis using multivariable Cox proportional hazards along with the log-rank test.

Results

There were 3820 patients included in this study, with 2385 (62%) having ILD-related inhalational exposure. Exposed patients were younger, particularly in the idiopathic pulmonary fibrosis subgroup. Inhalational exposure was associated with male gender (adjusted OR 1.46, 95% CI 1.28-1.68, p < 0.001) and family history of pulmonary fibrosis (adjusted OR 1.73, 95% CI 1.40-2.15, p < 0.001). Patients with any inhalational exposure had improved transplant-free survival (hazard ratio 0.81, 95% CI 0.71-0.92, p = 0.001); this effect persisted across diagnostic subtypes. The relationship between exposures and annual change in forced vital capacity varied by ILD subtype.

Conclusion

Patients with fibrotic ILD report high prevalence of inhalational exposures across ILD subtypes. These exposures were associated with younger age at diagnosis, male gender and family history of pulmonary fibrosis. Identification of an inhalational exposure was associated with a survival benefit. These findings suggest that inhaled exposures may impact clinical outcomes in patients with ILD, and future work should characterize the mechanisms underlying these relationships.

SUBMITTER: Lee CT

PROVIDER: S-EPMC9296585 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Inhalational exposures in patients with fibrotic interstitial lung disease: Presentation, pulmonary function and survival in the Canadian Registry for Pulmonary Fibrosis.

Lee Cathryn T CT Strek Mary E ME Adegunsoye Ayodeji A Wong Alyson W AW Assayag Deborah D Cox Gerard G Fell Charlene D CD Fisher Jolene H JH Gershon Andrea S AS Halayko Andrew J AJ Hambly Nathan N Khalil Nasreen N Kolb Martin M Lok Stacey D SD Manganas Hélène H Marcoux Veronica V Morisset Julie J Sadatsafavi Mohsen M Shapera Shane S To Teresa T Wilcox Pearce P Ryerson Christopher J CJ Johannson Kerri A KA

Respirology (Carlton, Vic.) 20220505 8

<h4>Background and objective</h4>Inhalational exposures are a known cause of interstitial lung disease (ILD), but little is understood about their prevalence across ILD subtypes and their relationship with pulmonary function and survival.<h4>Methods</h4>Patients with fibrotic ILD were identified from the multicentre Canadian Registry for Pulmonary Fibrosis. Patients completed questionnaires regarding ILD-related occupational and environmental exposures. The relationship between exposures and the ...[more]

PMID: 35512793

Similar Datasets

Project description:BackgroundInhalational exposures are increasingly recognized as contributing factors in interstitial lung disease (ILD). However, the characteristics of both exposures and exposed patients are not well understood. We hypothesized that domestic and occupational inhalational exposures would be common and associated with differences in demographics, clinical characteristics, and transplant-free survival in patients with all forms of ILD.Research questionWhat is the prevalence of inhalational exposures across all ILD diagnoses, and are these exposures associated with differences in demographics, clinical characteristics, and transplant-free survival?Study design and methodsPatients from a tertiary ILD clinic underwent an interview designed to capture inhalational exposures including occupational, home, hobbies, and tobacco. Demographic and survival data were collected from the electronic medical record. Survival analysis was performed using Cox regression to compare exposed vs unexposed patients and adjusted for gender-age-physiology score and smoking.ResultsOne hundred and fifty-six patients seen between May and October 2018 were analyzed. Patients had a wide variety of multidisciplinary diagnoses, with a minority of patients with hypersensitivity pneumonitis (14%). One hundred and one patients (65%) had potentially relevant inhalational exposures. More men than women had a history of any exposure (82% vs 51%; P < .001), occupational exposure (66% vs 14%, P < .001), and multiple exposures (56% vs 26%, P < .001), respectively. White race was associated with bird and hobby exposure. Patients with any exposure had worse transplant-free survival (unadjusted hazard ratio, 2.58; 95% CI, 1.13-5.92; P = .025), but this was not statistically significant after adjustment (hazard ratio, 1.82; 95% CI, 0.77-4.27; P = .17).InterpretationA standardized interview revealed most patients across all types of ILD had potentially relevant inhalational exposures. Exposures were markedly different based on demographics and were associated with worse transplant-free survival, but this survival difference was not significant after multivariable adjustment. Identification and avoidance of exposures represent actionable targets in ILD management.

Project description:BackgroundIdiopathic pulmonary fibrosis (IPF) is associated with increased expression of cyclin-dependent kinase inhibitors such as p16 and p21, and subsequent induction of cell cycle arrest, cellular senescence, and pro-fibrotic gene expression. We sought to link p16-expression with a diagnosis of IPF or other fibrotic interstitial lung diseases (ILDs), radiographic pattern, senescent foci-specific gene expression, antifibrotic therapy response, and lung transplant (LTx)-free survival.MethodsEighty-six cases of fibrosing ILD were identified with surgical lung biopsy. Immunohistochemistry for p16 was performed on sections with the most active fibrosis. p16-positive foci (loose collection of p16-positive fibroblasts with overlying p16-positive epithelium) were identified on digital slides and quantified. Cases were scored as p16-low (≤ 2.1 foci per 100 mm2) or p16-high (> 2.1 foci per 100 mm2). Twenty-four areas including senescent foci, fibrotic and normal areas were characterized using in situ RNA expression analysis with digital spatial profiling (DSP) in selected cases.ResultsThe presence of p16-positive foci was specific for the diagnosis of IPF, where 50% of cases expressed any level of p16 and 26% were p16-high. There was no relationship between radiographic pattern and p16 expression. However, there was increased expression of cyclin-dependent kinase inhibitors, collagens and matrix remodeling genes within p16-positive foci, and cases with high p16 expression had shorter LTx-free survival. On the other hand, antifibrotic therapy was significantly protective. DSP demonstrated that fibroblastic foci exhibit transcriptional features clearly distinct from that of normal-looking and even fibrotic areas.ConclusionsWe demonstrated the potential clinical applicability of a standardized quantification of p16-positive fibroblastic foci. This method identifies an IPF phenotype associated with foci-specific upregulation of senescence-associated and matrix remodeling gene expression. While these patients have reduced LTx-free survival, good response to antifibrotic therapies was observed in those who were treated.

Project description:BackgroundA number of genetic markers linked to familial pulmonary fibrosis predict differential survival in interstitial lung disease (ILD) patients. Although genetic testing is not performed routinely for ILD, family history commonly is obtained and may inform outcome risk.Research questionDoes survival vary between patients with and without self-reported familial pulmonary fibrosis?MethodsFamily history was acquired systematically for consecutive ILD patients who consented to clinical registry enrollment at the University of Texas Southwestern and the University of California at Davis. Patients were stratified by idiopathic pulmonary fibrosis (IPF) and non-IPF ILD diagnosis and were substratified by presence or absence of familial pulmonary fibrosis, defined as one or more additional affected family members. Transplant-free survival was compared using multilevel, mixed-effects Cox proportional hazards regression.ResultsOf the 1,262 patients included, 534 (42%) had IPF ILD and 728 (58%) had non-IPF ILD. Of those with non-IPF ILD, 18.5% had connective tissue disease, 15.6% had chronic hypersensitivity pneumonitis, and 23.5% had unclassifiable ILD. Familial pulmonary fibrosis was reported in 134 IPF ILD patients (25.1%) and 90 non-IPF ILD patients (12.4%). Those with familial IPF showed an 80% increased risk of death or transplantation compared with those with sporadic IPF (hazard ratio [HR], 1.8; 95% CI, 1.37-2.37; P < .001), whereas those with familial non-IPF ILD showed a twofold increased risk compared with their counterparts with sporadic disease (HR, 2.08; 95% CI, 1.46-2.96; P < .001). Outcome risk among those with familial non-IPF ILD was no different than for those with sporadic IPF ILD (HR, 1.27; 95% CI, 0.89-1.84; P = .19).InterpretationPatient-reported familial pulmonary fibrosis is predictive of reduced transplant-free survival in IPF and non-IPF ILD patients. Because survival among patients with familial non-IPF ILD approximates that of sporadic IPF ILD, early intervention should be considered for such patients. Until clinical genetic testing is widely available and provides actionable results, family history should be ascertained and considered in risk stratification.

Project description:BackgroundPatients with idiopathic pulmonary fibrosis (IPF) frequently have multiple comorbidities, which may influence survival but go under-recognised in clinical practice. We therefore report comorbidity, antifibrotic treatment use and survival of patients with IPF observed in the multi-national EMPIRE registry.MethodsFor this prospective IPF cohort, demographics, comorbidities, survival and causes of death were analysed. Comorbidities were noted by the treating physician based on the patient's past medical history or as reported during follow-up. Comorbidities were defined as prevalent when noted at enrolment, or as incident when recorded during follow-up. Survival was analysed by Kaplan-Meier estimates, log-rank test, and Cox proportional hazards models. Hazard ratios (HR) were adjusted for gender, age, smoking status and FVC at enrolment.ResultsA population of 3,580 patients with IPF from 11 Central and Eastern European countries was followed every 6 months for up to 6 years. At enrolment, 91.3% of patients reported at least one comorbidity, whereas more than one-third (37.8%) reported four or more comorbidities. Five-year survival was 53.7% in patients with no prevalent comorbidities, whereas it was 48.4%, 47.0%, 43.8% and 41.1% in patients with 1, 2, 3 and ≥ 4 comorbidities, respectively. The presence of multiple comorbidities at enrolment was associated with significantly worse survival (log-rank test P = 0.007). Adjusted HRs indicate that risk of death was increased by 44% in patients with IPF reporting ≥ 4 comorbidities at baseline compared with no comorbidity (P = 0.021). The relationship between number of comorbidities and decreased survival was also seen in patients receiving antifibrotic treatment (63% of all patients; log-rank test P < 0.001). Comorbidity as cause of death was identified in at least 26.1% of deaths.ConclusionsThe majority of patients with IPF demonstrate comorbidities, and many have comorbidity-related deaths. Increasing numbers of comorbidities are associated with worse survival; and this pattern is also present in patients receiving antifibrotic therapy.

Project description:IntroductionAmong the various types of progressive fibrosing interstitial lung diseases (PF-ILDs), substantial survival data exist for idiopathic pulmonary fibrosis (IPF) but not for other types. This hinders evidence-based decisions about treatment and management, as well as the economic modelling needed to justify research into new treatments and reimbursement approvals. Given the clinical similarities between IPF and other PF-ILDs, we reasoned that patient survival data from four major IPF trials could be used to estimate long-term survival in other PF-ILDs.MethodsWe used propensity score matching to match patients with IPF taking either nintedanib or placebo in the TOMORROW, INPULSIS-1, INPULSIS-2 and INPULSIS-ON trials to patients with PF-ILDs other than IPF in the INBUILD trial. Seven models were fitted to the survival data for the matched patients with IPF, and the three best-fitting models were used to generate informative priors in a Bayesian framework to extrapolate patient survival of the INBUILD population.ResultsAfter propensity score matching, the analysis included data from 1099 patients with IPF (640 nintedanib patients; 459 placebo patients) and 654 patients with other PF-ILDs (326 nintedanib patients; 328 placebo patients). Gamma, log-logistic and Weibull models best fit the survival of the matched patients with IPF. All three models led to consistent Bayesian estimates of survival for the matched patients with other PF-ILDs, with median rates of overall survival ranging from 6.34 to 6.50 years after starting nintedanib. The corresponding control group survival estimates were 3.42 to 3.76 years.ConclusionWe provide the first estimates of long-term overall survival for patients with PF-ILDs other than IPF, and our analysis suggests that nintedanib may prolong their survival. Our Bayesian approach to estimating survival of one disease based on clinical trial data from a similar disease may help inform economic modelling of rare, orphan and newly defined disorders.

Dataset Information

Inhalational exposures in patients with fibrotic interstitial lung disease: Presentation, pulmonary function and survival in the Canadian Registry for Pulmonary Fibrosis.

Background and objective

Methods

Results

Conclusion

Publications

Inhalational exposures in patients with fibrotic interstitial lung disease: Presentation, pulmonary function and survival in the Canadian Registry for Pulmonary Fibrosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets